The human erythrocyte carbonic anhydrase isoenzymes B and C function by catalyzing the reversible hydration of carbon dioxide to bicarbonate. It is proposed that this function be related to the detailed active-site structure of these zinc metalloenzymes through a combination of chemical modification and nuclear magnetic resonance approaches. The studies will encompass the complexes of these enzymes with their substrates and with their pharmacologically important sulfonamide inhibitors.